Ertapenem is one of the carbapenem antibiotics and its chemical name is (4R,5S,6S)-3-[(3S,5S)-5-[(3-carboxyphenyl)carbamoyl]pyrrolidin-3-yl]sulfanyl-6-(1-hydro xyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid. The chemical structure of ertapenem is as follow:

Ertapenem is a weakly crystalline solid, hygroscopic at ambient conditions, and is unstable at room and refrigerated temperatures. Ertapenem is prepared in large batches as a salt form, i.e., monosodium salt form. Because ertapenem is unstable at a temperature more than about −20° C., the bulk compound should be stored at low temperature (about −20° C.) to prevent degradation into dimer and open ring by-products. Although the unstable carbapenem after bulk manufacturing can be stored for long periods of time at a low temperature, the bulk compound should be converted into a stable formulation prior to use as once-a-day antimicrobial agent for intravenous (IV) and intramuscular (IM) administration. Currently, ertapenem is formulated into a lyophilized formulation, which is used as an injection form in clinical practices.
Korean Patent No. 10-0756595 has disclosed a process for preparing an ertapenem-containing lyophilized formulation including the use of carbon dioxide sources such as NaHCO3 as an additive. However, when a lyophilized formulation is prepared according to Korean Patent No. 10-0756595, ertapenem-derived degradation products are increased in the step for lyophilizing the solution containing the carbon dioxide sources such as NaHCO3 and the bulk compound, which results in lowering the amount thereof. And also, even when the obtained lyophilized formulation is stored at low temperature (about −20° C.), the stability thereof is also decreased due to degradation product formation.
Therefore, there is a need to develop a process for preparing a lyophilized formulation which can solve both the decreased purity during the lyophilizing step and the decreased stability of the obtained lyophilized formulation.